论文部分内容阅读
目的:观察FLT3抑制剂索拉非尼(sorafenib)联合三氧化二砷(AS2O3)对FLT3-ITD突变的人类急性双表型(B、单核)髓细胞白血病MV-4-11细胞增殖、细胞周期和凋亡的作用,为该联合用药方案的临床应用提供实验依据。方法:将对数生长期的MV-4-11细胞分为4组:空白对照组(不加药),索拉非尼单药(1、10、100、1 000、5 000、10 000 nmol/L)组,AS2O3单药(0.125、0.25、0.5、1.0、2.0μmol/L)组,索拉非尼+AS2O3联合用药(10 nmol/L+1.0μmol/L)组。CCK-8法检测索拉非尼和AS2O3单用或联用对MV-4-11细胞增殖的抑制作用,流式细胞术检测MV-4-11细胞的凋亡及细胞周期。结果:索拉非尼和AS2O3单用对MV-4-11细胞的增殖均有抑制作用,且均呈浓度依赖性;两药联用对MV-4-11细胞增殖的抑制率显著高于两药的单用[(70.72±1.03)%vs(47.24±1.27)%、(20.28±0.70)%;均P<0.01),两药相互作用指数(coefficient of drug interaction,CDI)为0.696,表现出协同作用。索拉非尼可使MV-4-11细胞周期阻滞于G0/G1期,两药联用阻滞得更严重。两药联合作用于MV-4-11细胞48 h后,MV-4-11细胞早期凋亡率显著高于两药单用(89.06%vs 68.27%、78.71%;均P<0.05)。结论:索拉非尼联合AS2O3能够协同抑制MV-4-11细胞的增殖,并且比单药作用更有效地阻滞细胞周期于G0/G1,更明显地促进细胞凋亡。
AIM: To investigate the effects of FLT3 inhibitor sorafenib combined with arsenic trioxide (AS2O3) on the proliferation, cell cycle and apoptosis of FLT3-ITD mutant human acute dual phenotype (B, mononuclear) myeloid leukemia MV-4-11 cells The role of death, for the clinical application of the combination program to provide experimental evidence. Methods: The logarithmic growth phase of MV-4-11 cells were divided into 4 groups: blank control group (without drug), sorafenib alone (1,10,100,1 000,5 000,10 000 nmol / L group, AS2O3 single group (0.125,0.25,0.5,1.0,2.0μmol / L) group, sorafenib + AS2O3 combination group (10 nmol / L + 1.0μmol / L) group. The inhibitory effect of sorafenib and AS2O3 alone or in combination on the proliferation of MV-4-11 cells was detected by CCK-8 assay. The apoptosis and cell cycle of MV-4-11 cells were detected by flow cytometry. Results: Sorafenib and AS2O3 alone inhibited the proliferation of MV-4-11 cells in a concentration-dependent manner. The inhibition rate of MV-4-11 cells was significantly higher than that of both (70.72 ± 1.03)% vs (47.24 ± 1.27)%, (20.28 ± 0.70)%, all P <0.01). The coefficient of drug interaction (CDI) between the two drugs was 0.696, Synergy. Sorafenib can block the MV-4-11 cell cycle in the G0 / G1 phase, the combination of the two drugs even worse. The early apoptosis rate of MV-4-11 cells was significantly higher than that of the two drugs alone (89.06% vs 68.27%, 78.71%; both P <0.05) after 48 hours treatment of MV-4-11 cells. CONCLUSION: Sorafenib combined with AS2O3 synergistically inhibits the proliferation of MV-4-11 cells and arrests cell cycle at G0 / G1 more effectively than monotherapy, and promotes apoptosis more obviously.